Mar-Apr 2001
Aminolysis of Phosphorus Heterocycles Incorporating an α-Aminoamide Moiety. III
479
1
NMR (CDCl ): + 21.27; H (CDCl ): δ 7.8 - 7.5 (m, 5H, C H PO),
1,3-Diphenylsulfonyl-2-oxo-2-methyl-1,3,2-diazaphospholidine (4f).
3
3
6 5
7.24 (s, 10H, 2 CH C H ), 4.2 (dd, J ~ 9 and 6 Hz, 4H, 2 CH ).
2
6
5
2
The reaction was completed after two days (66 % of reaction
after one day). After completion, only one extraction was per-
Phenyl Phosphonic Acid bis-N-Phenylsulfonylethylenediamide,
Isopropylammonium Salt (9).
formed, at ~ 10°, with brine. IR: NH bands not observed, ν SO
2
-1 1
1359, 1175, PO 1249 cm ; H (CDCl ): δ 8 - 7.5 (2 m, 4H + 6H, 2
3
To a solution of heterocycle 4a (157 mg, 0.34 mmole) in acetoni-
trile (0.3 g) were added first isopropylamine (0.3 g, 5.07 mmoles,
15 equivalents), then isopropanol (0.3 g, 15 equivalents) and finally
after two weeks, under stirring (emulsion), 0.4 g of water. The
NMR spectra showed 10 % and 100 % of conversion into the salt 9
respectively before and 4 days after addition of water. After concen-
tration to dryness the residue was recrystallized from acetonitrile
yielding 160 mg (87 %) of the product, mp 180-182°. IR: ν NH
3370, NH 2620, 2580, SO 1325, 1160, PO 1190 cm ;
(DMSO-d ): δ 7.7 - 7.45 (m, 18H, 3 C H + NH + NH), 3.3 - 2.85
(2 mf, 5H, 2 CH + CH), 1.15 (d, J ~ 8 Hz, 6H, 2 CH );
(DMSO-d ): δ positive values: 3 C quat: δ 142.98, 141.20, 139.83
(d, J = 172.77 Hz, C ipso); 2 CH : 46.27, 43.86; negative values:
ten CH signals (expected: eleven), CH: 43.66, CH : 21.15.
C H ), 3.6 - 3.17 (2 m, 4H, 2 CH ), 2.41 (d, J = 17.53 Hz, 3H,
6
5
2
13
CH ); C (CDCl ): δ 137.37 (2 C quat.), 134.09 (2 C para), 129.4
(4 C meta or ortho), 128.20 (4 C ortho or meta), 43.63 (d, J = 5.23
Hz, 2 CH ), 19.56 (d, J = 119.58 Hz, CH ); mass spectrum, relative
3
3
31
P
2
3
intensity: 418, 100 % (M + NH ), 401, 5 % (M + H).
4
Anal. Calcd. for C
H N O PS (400.40): C, 44.99; H, 4.28;
15 17 2 5 2
N, 6.99. Found: C, 44.04; H, 4.07; N, 6.93.
+
-1 1
1,3-Dimethylsulfonyl-2-oxo-2-methyl-1,3,2-diazaphospholidine
(4g).
H
2
2
+
6
6
5
2
13
C
2
3
The reaction was completed after ~ 10 hours. For the separa-
tion activated 4 Å molecular sieves and anhydrous potassium car-
bonate (respectively 7.5 and 5.3 g for 7.5 mmoles of dissulfon-
amide 1b) were added and left under vigorous stirring for 3
hours. The insolubles were filtered off, the filtrate concentrated to
dryness, and the product crystallized at ~ 15°. Without addition
of molecular sieves complete hydrolysis took place. IR: NH
6
2
3
Anal. Calcd for C
H N O PS (539.6): C, 51.20; H, 560; N,
23 30 3 6 2
7.70. Found: C, 50.80; H, 5.59; N, 7.73.
Methylphosphonic Methylamide (6g).
-1
1
bands not observed, ν SO 1356, 1157, PO 1238 cm ;
H
2
Similarly with heterocycle 4g in the presence of a large excess
of methylamine in a mixture of chloroform, dimethylformamide,
pyridine (2.7:1:0.3) a complete reaction took place in less than a
day. The solution was concentrated to dryness and the residue
triturated in deuterochloroform leaving an insoluble material. H
NMR analysis of the residue dissolved in DMSO-d and of the
(DMSO-d ): δ 3.76 (m, 4H, 2 CH ), 3.27 (s, 6H, 2 CH SO ),
6
2
3
2
13
2.03 (d, J = 17.46 Hz, 3H, CH PO); C (DMSO-d ): δ 43.06 (d,
3
6
J = 5.08Hz, 2 CH ), 40.3 (2 CH SO ), 17.64 (d, J = 118.34 Hz,
2
3
2
CH PO); mass spectrum, relative intensity: 294, 100 % (M +
3
1
NH ); cryoscopy in DMSO: calcd.: 276, found: 214.
4
6
Anal. Calcd. for C H N O PS (276.26): C, 21.74 ; H, 4.74 ;
5
13
2
5
2
filtrate showed, respectively, diamide 1b and a mixture of 1b and
N, 10.14. Found: C, 21.65; H, 4.69; N, 10.14.
1
6g (major product). H-NMR (DMSO-d ): δ 2.32 (dd J = 12.01
6
1,3-Dimethylsulfonyl-2-oxo-2-phenyl-1,3,2-diazaphospholidine
(4h).
and 4.5 Hz, 6H, 2 NCH ), 1.23 (d, J = 15.19 Hz, 3H, CH ). After
3
3
31
addition of D O the product is nearly exclusively extracted.
(D O): δ + 39.5; C (D O): 27.89 (2 NCH ), 13.72 (d, J =
P
2
13
The reaction was completed in less than a week, at 80° (78 %
2
2
3
112.31 Hz, CCH ).
of reaction after three days). IR: NH bands not observed, ν SO
3
2
-1
1
The same diamide 6g was also obtained from heterocycle 4f in
less than a week in the presence of a large excess (25 equivalents)
in chloroform. After concentration to dryness a quantitative yield
of a mixture of dissulfonamide 1a and phosphodiamide 6g was
obtained. After trituration in deuterochloroform the ethylene
1357, 1156, PO 1238 cm ; H (DMSO-d ): δ 7.9 - 7.6 (m, 5H,
6
13
C H ), 4 -3.9 (m, 4H, 2 CH ), 3.17 (s, 6H, 2 CH ); C (DMSO-
6
5
2
3
d ): δ 133.1 (C para), 132.06 (d, J = 12.18 Hz, 2 C meta), 129.51
6
(d, J = 169.54 Hz, C ipso), 128.47 (d, J = 16.1 Hz, 2 C ortho),
44.3 (d, J = 5.28 Hz, 2 CH ), 40.22 (2 CH ); mass spectrum, rel-
2
3
1
diamide 1a was isolated by filtration with a 55 % yield. H NMR
ative intensity: 356, 100 % (M + NH ), 339 1 % (M + H).
4
analysis of the filtrate showed the characteristic signals of 6g
with those of 1a (~ 0.5 equivalents).
Anal. Calcd. for C
H N O PS (338.33) : C, 35.5 ; H, 4.47 ;
10 15 2 5 2
N, 8.28. Found : C, 35.83 ; H, 4.36 ; N, 8.34.
III. Aminolysis of Heterocycles 4.
Phenylphosphonic Dibenzylamide (6a).
Illustrative Procedure.
A first control experiment using methane phosphonic dichloride
reacted with two equivalent of dry methylammonium chloride and
four equivalents of triethylamine in dichloromethane showed traces
of the product [cf. ref. 10]. A second experiment with slow addition
of the dichloride to a cold (0°) solution in pyridine of excess
methylamine showed a rather selective reaction, the expected prod-
uct 6g accounting for 60 % of the total phosphorus content. The
pure product was separated by tetrahydrofuran (THF) extraction of
the residue obtained after concentration to dryness of the reaction
mixture with two equivalents of sodium hydroxide.
A solution of the heterocycle 4a (104 mg, 0.22 mmole) and ben-
zylamine (0.22 g, 2.05 mmoles, 9.3 equivalents) in anhydrous ace-
tonitrile (1.2 g) was heated at 70°, with exclusion of moisture, until
31
complete disappearance (one week) in the P NMR spectrum of the
signal of 4a. Two products δ + 20 (80 %, 6a) and + 10 (20 %, salt
related to 9) were then observed. After concentration to dryness, the
residue was triturated in a 10 % solution of citric acid (a few ml) and
the insoluble material, free of the salt, was filtered, dried and dis-
solved in boiling methanol (a few ml). After standing overnight at
room temperature the crystaline dissulfonamide 1a (mp 168-170°)
was isolated by filtration (80 mg, quantitative yield). The filtrate was
IV. Alcoholysis of Heterocycles 4.
Dimethylphenylphosphonate (8a).
Illustrative Procedure.
A solution of the heterocycle 4a (1.38 g, 3 mmoles) in
concentrated to dryness and 6a was crystallized from ethylacetate
methanol (20 ml) containing DBU (a few drops) was kept at
room temperature for 3 weeks. The P NMR spectrum showed
31
31
(0.5g): 30 mg (40% yield) mp 95-97° (lit [6] mp 100-101°).
P